Pluripotency Factor Tex10 Finetunes Wnt Signaling for PGCLC Specification and Spermatogenesis

The appropriate specification and differentiation of primordial germ cells (PGCs) are critical in promoting human reproductive health. This study establishes the testis-specific transcript 10 (Tex10) as a previously unappreciated molecular player in PGC specification in culture. Mechanistically, Tex10 binds the Wnt negative regulator genes marked by H3K4me3 at the PGCLC stage in restraining Wnt signaling. Tex10 depletion hyperactivates Wnt signaling compromising the specification efficiency, whereas Tex10 overexpression attenuates the Wnt signaling promoting efficient PGC specification. We also explored the in vivo roles of Tex10 in germ cell development using the Tex10 conditional knockout mouse model, revealing compromised male fertility with reduced sperm number and motility. In addition, defective spermatogenesis in Tex10 knockout mice is correlated with aberrant Wnt signaling upregulation. Taken together, our study uncovers a new role of Tex10 in PGC specification and male germline development through finetuning the Wnt signaling.